The pemetrexed-containing treatments in the non-small cell lung cancer, is -/low thymidylate synthase expression better than +/high thymidylate synthase expression: a meta-analysis

Abstract

BackgroundThe predictive value of thymidylate synthase (TS) for clinical sensitivity to pemetrexed-containing chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis is performed to provide an assessment of whether expression variations of TS are associated with objective response in patients with NSCLC treated with pemetrexed-containing chemotherapy.MethodsAn electronic search was conducted using the databases MEDLINE, EMBASE and CNKI, from inception to June 10th, 2013. A systemic review of the studies on the association between TS expression in NSCLC and objective response of pemetrexed-containing regimen was performed. Pooled odds ratios (OR) for the response rate were calculated using the software Revman 5.0.ResultsThere were a total of 526 patients in the eight studies that met our criteria for evaluation. +/high expression of TS was found in 269 patients (51.1%), and -/low expression for this gene was found in 257 (48.9%) patients. The objective response rate for pemetrexed-containing chemotherapy was significantly higher in patients with -/low expression TS expression (OR = 0.45; 95% CI, 0.29–0.70; p = 0.0004). Although patients with -/low expression of TS have a longer median overall survival time and progression free survival time than those with +/high expression of TS, the difference was not statistically significant.Conclusions−/low expression of TS was associated with higher objective response in NSCLC patients treated with pemetrexed-containing chemotherapy. TS may be a suitable marker of sensitivity to pemetrexed-based chemotherapy in patients with NSCLC.

Association between certain non–small cell lung cancer driver mutations and predictive markers for chemotherapy or programmed death‐ligand 1 inhibition

“…12 The low expression rate of ERCC1, RRM1, TS and β-tubulin III, and the PD-L1 positive rate, differing from other studies, might be due to, for instance, different races, proportions of histology and stages. [13][14][15] In particular, the issue of ERCC1 isoform and PD-L1 antibody selection for IHC is worth mentioning. Friboulet et al 16 detected and elaborated on the function of ERCC1 isoform 202 for nucleotide excision repair and cisplatin resistance.…”

Efficacy of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion–Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations in East Asian Populations

“…Low level of TS expression has been considered a favorable marker for the efficacy of pemetrexed in NSCLC 33,35 and lung adenocarcinoma. 34 Our findings showed a very low TS level (median TS H-score of 55) in lung adenocarcinomas, which was similar to that in a previous report.…”

“…[25][26][27][28][29] Interestingly, novel ROS1 fusion-positive tumors, which share similar clinical characteristics with ALK fusion tumors, 30 were also recently reported as having longer PFS and higher response rates. 16,[31][32] Although prior reports suggested that TS expression levels were inversely correlated with the response to pemetrexedbased chemotherapy in NSCLC, [33][34][35] the correlation of TS expression level with the length of response during pemetrexed chemotherapy is still controversial in NSCLC tumors with different molecular alterations (e.g., EGFR mutation, EML4-ALK fusion, ROS1 fusion, and wild type). 24,26,27,31 The interaction between these driver mutations and the duration of pemetrexed-associated benefits has recently attracted considerable attention.…”

A Randomized Phase 2 Study of Gefitinib With or Without Pemetrexed as First-line Treatment in Nonsquamous NSCLC With EGFR Mutation: Final Overall Survival and Biomarker Analysis

“…To optimally balance the number of patients in the subgroups, due to the small sample size and 2:1 randomization, the cutoff point for low versus high TS expression was the median H score for the study population evaluable for TS. 32 Treatment-emergent adverse events (AEs) were reported according to the Medical Dictionary for Regulatory Activities (version 18.0) and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).…”